In an autoimmune reaction, immune cells, such as T cells, attack the body's own healthy tissues by mistake. The basis for this is a breakdown of T cell immune tolerance. Among the organs that can be affected by autoimmune reactions, the skin is specifically plagued by those misguided reactions against self-tissues. The current application is designed to elucidate the mechanisms that control in vivo T cell reactions directed at a skin-restricted antigen and their role in skin autoimmunity. Specifically, the candidate will analyze two main types of T cells involved in an autoimmune response: pathologic effector T cells and protective regulatory T cells. The balance between those two types of T cells determines the outcome of an immune reaction. Research will focus on uncovering mechanisms of differentiation and maintenance of these effector and regulatory T cells in the skin. Specifically, the candidate will investigate (1) early events in the immune reaction when the T cells make initial contact with the self-antigen and define the conditions that favor the generatio of regulatory T cells and (2) late events that influence the maintenance of regulatory versus effector T cells in the skin. The candidate will utilize a novel mouse model that she has recently established. That model of skin autoimmunity allows to meticulously dissect individual mechanisms and signals that control T cell responses during the course of an autoimmune reaction. Understanding how stimulatory signals during antigen-contact impact differentiation, survival, and maintenance of regulatory T cells in tissues will provide a foundation for future work aimed at skewing the balance between regulatory and effector T cells in the skin. The long-term goal is to therapeutically interfere with the activation, generation and maintenance of regulatory T cells to treat autoimmune and chronic inflammatory skin disease.